The objective of this research is to correlate active chloride transport across the cornea with membrane molecular composition and changes reflecting modifications of its fluidity. In preliminary experiments we have found that certain unsaturated fatty acids are able to enhance C1 transport (as measured by short-circuit currents and isotope fluxes) across frog and rabbit corneas when these are incorporated into the cell membranes of corneal epithelium. By substituting selected fatty acids into membrane phospholipids, we are able to change membrane composition and the physical properties of corneal cell membranes. We have found, for example, that linoleic acid enhances corneal C1 transport and also increases corneal cell membrane fluidity. A model is presented that will explain the relationship between transport phenomena and membrane fluidity, based on the lateral mobility of membrane-bound enzymes and receptors (cuatrecases 1974). According to this model the rate of enzyme-receptor interaction depends upon membrane lipid fluidity and therefore membrane fluidization should result in the enhancement of c-AMP synthesis. A test of the validity of this model will be one of the objectives of this program. By investigating the full range of fatty acids available to us and other agents known to alter membrane fluidity, we will attempt to characterize and better define the cellular mechanisms responsible for the activation of trans-corneal C1 transport by fatty acids. The molecular changes in the membranes of the cornea have direct relationship to the phenomena of corneal transparency, penetration of drugs and sensitivity of the corneal epithelium.